An Analytical Expression for the Regulation of Ventricular Volume in the Normal and Diseased Heart

Abstract

There is increasing interest in the literature indicating that the volumetric regulation of the left ventricle (LV) and the right ventricle (RV) may be conveniently represented in a graph relating end-systolic volume (ESV) to end-diastolic volume (EDV). This view contrasts with the classical description by Starling's law, which for decades has dominated the analysis of volumetric input–output relationships of the heart. In the present study we critically survey the existing evidence for a graphical representation emphasizing the role of ESV rather than stroke volume (SV) as the dependent variable in the description of cardiac function. Mostly a linear relationship between ESV and EDV has been documented. This concept is now applied both in the study of a particular heart under consideration and in a population-based approach. We analyzed volumetric data obtained from human patients, instrumented conscious dogs, and healthy horses, and found linear relationships for volume and diameters. A distinct parallel leftward shift of the regression curve is found to be commensurate with diminished parasympathetic activity, whereas a clockwise rotation of the curve is associated with decreased sympathetic activity. The ensuing changing patterns of the ESV vs. EDV relationship have implications for ejection fraction, for which we derived an analytical formula to account for such dependence. Thus, the analytical expression of ESV vs. EDV provides a functional representation of factors regulating LV and RV volume. The new approach applies to both health and disease states, and is shown to be invariant for afterload variation, in contrast to the Starling curve. Moreover, it appears typically sensitive to various types of interventions, including those affecting chronotropic and inotropic state.